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Biomedical subjects

P Leger

Publications and source records attributed to P Leger.

At least 19 recordsLinked to original sources

Sheep blood polymorphism and genetic divergence between French Rambouillet and Spanish Merino: role of genetic drift.

Rambouillet sheep originating from Spanish Merino have been maintained in France as a small and closed flock since their importation. After 190 years of independent evolution, the flock has markedly differentiated from its Spanish parental population. The observed differences between them were characterized by the fixation in Rambouillet of the Mb and F30 alleles, which occurred in Spanish Merino with frequencies of 0.90 and 0.80 respectively (at two distinct blood group loci M and F30) and by the absence in Rambouillet of other alleles or phenogroups (at the Tf and the A, B, C blood group loci) which were observed in Spanish Merino with frequencies ranging from 0.10 to 0.28. On the basis of their phenotypic distributions at 11 blood polymorphic loci, the two populations differed significantly from each other (total chi 2 values = 352.62, 23 df, P less than 0.001). By comparing the observed magnitude of gene frequency differences between Rambouillet and Spanish Merino with the estimate of inbreeding coefficient for Rambouillet obtained from pedigrees, it appeared that the observed genetic differences could be attributed to the evolutionary change due to random drift in the small and closed flock of Rambouillet.

Animals

Heart transplantation: update.

Clinical application of heart transplantation goes beyond 25 years experience. The main indications for cardiac transplantation remain idiopathic cardiomyopathies and ischemic diseases. To obtain a suitable donor has become progressively more difficult due to the increase of transplants performed and the shortage of donors. Advances in the detection of early rejection, improved organ preservation procedures, and the introduction of new immunosuppressive therapy protocols have produced dramatic results in heart transplantation. Late graft atherosclerosis remains a serious threat despite retransplantation and, in some cases, mechanical cardiac support.

Adolescent

Heart and heart-lung transplantation in the 1990s.

After 22 years of clinical application in our unit, heart transplantation is now an accepted therapeutic method. Its indications are well established, its surgical technique and post-operative control and treatment well defined, mostly due to better diagnosis of the rejection episodes with the aid of echocardiography and endomyocardial biopsy and the use of cyclosporin. The results are remarkable with a survival rate of 70% at 5 years, and a full rehabilitation into family, social and often professional life for almost all the survivors. Its use has dramatically changed the prognosis of patients with irreversible cardiac failure but underlines the lack of a sufficient number of donors' hearts. The heart-lung transplantation, making use of the progress of heart transplantation, has been used successfully since 1982 and for the first time in Europe by our group. Improvement in the selection of recipients, lung preservation, surgical technique and post-operative management have brought a new and real hope to patients not only irreversible cardiopulmonary lesions but also terminal pulmonary disease.

Heart Transplantation

Survival prediction in staged heart transplantation using Jarvik-7 artificial heart.

BACKGROUND: Because mechanical circulatory assist as a bridge to heart transplantation places a further strain on current donor shortage as well as on medical cost containment, safe and effective use of the device is essential. METHODS AND RESULTS: To predict survival before undertaking staged heart transplantation with the Jarvik-7 artificial heart, our 58 attempts were reviewed retrospectively. Scores of 1-4 were given for six preoperative factors based on results obtained by univariate and multivariate analyses between survivors and nonsurvivors of staged heart transplantation: transplant rejection (scored 4: S4) or postoperative heart failure (S3) as the indication, recipient height < 175 cm (S3), body surface area < 1.8 m2 (S3), hyperbilirubinemia > 24 microM/l (S2), weight < 60 kg (S2), and age > 40 years (S1). Of 14 survivors, 13 had a total score < 4 (sensitivity, 93%), with an average score of 1.6 in contrast to 5.5 for 44 nonsurvivors (p < 0.001). Among 26 patients scored < 4, 21 had heart transplantation, of whom 13 left the hospital. Of 32 patients scored > or = 4, only four could be discharged after transplantation (specificity, 70%). CONCLUSIONS: Multiple preoperative factors successfully predicted transplantability and survival in staged heart transplantation. The results underscore the importance of preoperative condition and patient selection to achieve successful and effective use of Jarvik-7 as a bridge to heart transplantation.

Actuarial Analysis

Chronic liver dysfunction in heart transplant recipients, with special reference to viral B, C, and non-A, non-B, non-C hepatitis. A retrospective study in 80 patients with follow-up of 60 months.

In order to assess the prevalence, causes, and severity of chronic liver dysfunction (LD) in heart transplant patients, 80 transplanted patients followed for 60 months (median; range, 1.5-98 months) were reviewed. Sustained liver dysfunction was found in 50 patients, occurring during the first year after heart transplantation in 42 (84%) of them. Most patients were asymptomatic (80%). Causes for the liver dysfunction included non-A, non-B hepatitis in 16 cases (32%), viral B hepatitis in 13 (26%), delta hepatitis in one (2%), drug-induced hepatitis in six (12%), and cardiac failure in seven (14%). Anti-HCV antibodies were found in 56.2% of patients with non-A, non-B hepatitis and in 22% of patients with HBV hepatitis. It was found neither in patients with drug-induced hepatitis cardiac failure nor in patients with normal liver tests. This study outlines a high prevalence of LD (62.5%) in heart transplant patients, the high frequency of viral-related chronic LD (usually of moderate severity), and high incidence of HCV and HBV hepatitis.

Adolescent

Prognostic indices of survival in patients supported with temporary devices (TAH, VAD).

In an attempt to identify current indications and patient selection criteria for the use of mechanical circulatory support, we reviewed our experience in 83 patients who received a total artificial heart (TAH; n = 43), ventricular assist device (VAD) (n = 13), centrifugal pump (n = 17) or extracorporeal membrane oxigenation (ECMO) (n = 8) as a bridge to transplantation (Group I, n = 50) or for recovery from heart failure (Group II, n = 33). Comparing patients successfully transplanted (n = 20) or weaned (n = 9) who survived initial hospitalization, and those who died on mechanical support, there were no differences in preoperative renal, hepatic or pulmonary functions. Postoperative urinary output and bilirubin levels were the earliest variables affecting survival, and urinary output 24 hours after implant was discriminative in patients who survived (p less than 0.01). Age (above or below 40 years) and modality of terminal heart failure (acute versus chronic) were the most important factors affecting survival in the bridge to transplant group: 82% of young patients with acute decompensation were transplanted and 63% are long-term survivors while all patients over 40 years with chronic heart failure died on mechanical support (MS). In postcardiotomy patients, duration of cardiopulmonary by-pass (CPB) was significantly different comparing survivors with those who died in either bridge or recovery groups and all patients who had a CPB greater than 4 hours died on MS or after transplantation or weaning. In conclusion, preoperative indices indicating reversibility of multiple organ dysfunction remain to be identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Atrial natriuretic peptide level and intracardiac pressure in cardiac transplant recipients.

Blood pressures and plasma atrial natriuretic peptide (ANP) concentrations have been measured in venous and intracardiac sites in 11 patients (10 men and 1 woman) given cardiac transplants. The mean plasma ANP level was 214.4 pg.ml-1 in the superior vena cava and 281 pg.ml-1 in the right atrium. This significantly higher level was maintained in the right ventricle (269) and in the pulmonary artery (295). The level in controls was 25 pg.ml-1. Intra cardiac and mean arterial pressures were in normal range in all patients, and there was no correlation between plasma ANP level and intracardiac pressure. The data suggest that in cardiac transplant patients right atrial pressure does not have a primary role in releasing ANP. The transplanted heart is denervated and remains so for many months after operation, thus suggesting that innervation is not obligatory for ANP secretion. Further studies are required to determine the relative contribution of donor and recipient atrial tissues to ANP secretion.

Atrial Natriuretic Factor

Approach to advanced aortic root infection.

Among our first 11,620 cases of valvular replacement, we observed 285 cases of valvular endocarditis and 59 cases (20.7%) in which the importance of the infectious lesions of the aortic or mitral annulus required complex valvular repair. In 23 patients with aortic valvular endocarditis, the presence of an abcess of the aortic annulus required its closure with a patch resulting in one early and one late death and five reinterventions with one death. Twenty patients are alive and well, 1 to 9 years after operation. In 11 patients, the extent of annular abcesses required the insertion of a subcoronary valved conduit. After a maximum follow-up of 8 years there were two early deaths, two late deaths, one reoperation, and seven good results. Twelve patients had a supracoronary valved conduit resulting in four early deaths, one late death, and two reoperations; seven are alive and well, 2 to 6 years later. Three patients previously operated on had a left ventricular abdominal aorta valved conduit, two of them are alive and well up to 6 years later. Severe infectious lesions of the valvular rings (aortic root) can require complex repairs that can be lifesaving and provide excellent long-term results.

Abscess

Effects of methylphenidate on early adolescent growth.

Thirty-one hyperactive adolescents treated with methylphenidate for at least 6 months demonstrated no significant deviation from expected height and weight growth velocities. In contrast to findings in prepubertal children, these results suggest that early adolescent growth is insensitive to methylphenidate.

Adolescent

[Cardiac surgery in patients over 80 years of age. Experience of a series of 51 patients].

Between January 1980 and June 1988, 51 patients over 80 years of age underwent open heart surgery at the La Pitié hospital (26 women and 25 men; average age 82 +/- 2 years, range 80-90 years). The cardiac pathology was calcific aortic stenosis (AS) in 40 cases, associated with coronary artery disease in 7 cases, mitral valve prolapse in 3 cases, coronary artery disease alone in 6 cases [complicated by a post-infarction ventricular septal defect (VSD) in one patient] or associated with aortic regurgitation in 1 case, and degeneration of an aortic bioprosthetic valve in 1 case. Forty patients (78%) were in Stage III or IV or the NYHA Classification. There was no other major pathology associated with the cardiac disease. Aortic valve replacement (AVR) was carried out in 42 patients, with a bioprosthetic valve in 38 patients. This procedure was associated with coronary bypass surgery in 7 cases and carotid artery surgery in 1 case. A mitral bioprosthesis was implanted in 2 patients and mitral valvuloplasty was carried out in 1 patient. An isolated myocardial revascularisation procedure was performed in 5 cases; the VSD was closed in 1 case. The hospital mortality was 17.6 per cent (9 patients). All deaths were of cardiac origin. Eleven patients had no postoperative complications at all. The 3 year survival rate of those who survived surgery was 71 per cent. Of the current 31 survivors, 29 are in Stage I or II of the NYHA Classification. These results suggest that surgery can be offered to octogenarians with invalidating cardiac disease alone carrying a poor short term prognosis.

Actuarial Analysis

Factors affecting survival in total artificial heart recipients before transplantation.

To identify factors affecting the successful bridge to transplantation, experience with 32 recipients of the Jarvik-7 artificial heart was reviewed. Between patients with and without a successful bridge, there were no significant differences in preoperative hepatorenal function or postoperative hemodynamics, but there were significant differences in body size. When recipients were divided according to body surface areas of less than or greater than 1.8 m2, the smaller patients more frequently developed respirator dependence (73% vs. 18%, p less than 0.01), renal failure (53% vs. 18%, p less than 0.05), and hepatic failure and sepsis, resulting in less frequent qualification for transplantation (20% vs. 65%, p less than 0.05). There were no successful bridge operations in seven patients with body surface areas of less than 1.7 m2, and only one success in nine patients who were less than 170 cm in height, despite use of a smaller stroke volume model. The smaller patients had poorer ventricular filling, which was largely compensated for by the drive controls set for significantly longer diastole and higher vacuum, resulting in similar hemodynamics between the groups. The results suggest that device fitting as manifested by body size is an important factor affecting major organ recovery and subsequent transplantation in recipients of the Jarvik-7 artificial heart. A paracorporeal device may be advisable for patients with body surface areas of less than 1.8 m2 or who were less than 175 cm in height until an even smaller model with a better fit in the thorax becomes available.

Adult

Heart transplantation: La Pitié experience, 1968-1989.

Heart transplantation is now an accepted therapeutic modality for end-stage heart disease. However, better immunosuppressive treatments and new methods to monitor rejection or detect early atherosclerosis must be developed to improve the long-term results after heart transplantation.

Cardiomyopathies

Total artificial heart: survival and complications.

A total artificial heart was implanted in 28 patients as a bridge to transplantation. Mean time of mechanical support was 14.8 +/- 10 days. The 70-mL Jarvik-7 was used in 12 patients and the 100-mL Jarvik-7 in the remaining 16. No clinical thromboembolic complications occurred during implantation. There was no postoperative bleeding requiring operation. Both survival and the rate of complications were similar in the two Jarvik-7 groups. Eleven patients underwent successful transplantation, and 1 patient is still on mechanical support. Sepsis and multiple-organ failure were the most important causes of death. All patients receiving the total artificial heart for severe acute rejection after transplantation died of infection. Early implantation of the total artificial heart is advised in younger patients and in older patients with acute cardiac failure. The use of this device should be contraindicated in immunosuppressed patients because of the high risk of infection.

Adult

Current problems in cardiac transplantation.

Since our initial orthotopic heart transplant (OHT) in 1968, the first in Europe, 1130 patients with ages ranging from 1 month to 66 years have been referred to us. The cause of irreversible myocardial damage was idiopathic cardiomyopathy in 74%, ischemic heart disease in 19% and left ventricular failure after valvular replacement in 7%. A total of 540 transplantations, 463 orthotopic, 40 heterotopic and 37 heart-lungs were carried out. Features of the early post-operative course include temporary (first week) cardiac instability treated by isoproterenol. Later complications included rejection (95%) and side-effects of immunosuppressive therapy; infection (83%), osteoporosis, malignancy, graft atherosclerosis (2%). Cyclosporine (Cy) was responsible for diastolic hypertension, renal dysfunction, hirsutism, hyperplasia of the gingiva, hepatic dysfunction, and seizures. The survival rate of the Cy-treated patients was 68% at 7 years. All survivors have virtually normal social and professional lives, included the longest survivor 14 years after the operation. Recently in 34 patients in acute irreversible cardiac failure and who cannot have a transplant in time, we implant a total artificial heart (TAH) type JARVIK 7 during a period from 1-150 days. There has been no mechanical failure, hemolysis or thrombo-embolism and only one right ventricular device malposition; 20 patients died before transplantation, 13 were successfully transplanted, 1 is still on the artificial heart. Heart transplantation, and TAH used as a bridge to transplantation are now an accepted therapeutic means for irreversibly cardiac failure in selected patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart Transplantation

Respiratory effects of the Jarvik-7 artificial heart.

In five anesthetized patients with a Jarvik-7 artificial heart, pulmonary volume displacements generated by cardiogenic oscillations were measured using an indirect spirometric method. Consequences on gas exchange were also evaluated during a 15-min period of apnea by use of a tracheal insufflation of pure O2 at a constant flow rate of 20 l/min. The Jarvik-7 artificial heart generated a mean pulmonary volume displacement of 105 +/- 29 (SD) ml/heart beat. After 15 min of apnea, arterial PCO2 (PaCO2) significantly increased from 29 +/- 5 to 47 +/- 6 (SD) Torr. PaCO2 increased by 0.8 Torr/min from the 5th to the 15th min of apnea. Mean arterial PO2, mean pulmonary shunt, mean O2 consumption, and mean metabolic production of CO2 did not change significantly during the apnea period. Because cardiac output was kept constant during the study, O2 transport was adequately maintained throughout the apnea period. In patient 1, where the period of apnea was continued for 60 min, PaCO2 progressively increased until the 45th min and then remained stable at 61 Torr during the last 15 min of apnea. This "plateau" corresponded to an alveolar ventilation of 3,907 ml/min, representing 69% of the alveolar ventilation calculated during conventional mechanical ventilation. In conclusion, the Jarvik-7 artificial heart provides a potent respiratory support through the cardiogenic oscillations it generates.

Adult

Heart transplantation: update.

Clinical application of heart transplantation goes beyond 20 years of experience. The results achieved on the first 8,000 transplanted patients are impressive with a 70% survival rate at 7 years of follow-up. Indications for transplantation are less restrictive and include diabetics and patients older than age 60. Pulmonary hypertension still remains difficult to define. Immunosuppressive therapy, now including OKT3 monoclonal antibody in addition to conventional drugs and cyclosporine, lessened the frequency and severity of rejection and infection but still need improvements. Late graft arteriosclerosis remains a serious threat despite the use of retransplantation and, in some cases, mechanical cardiac support.

Adult